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The Modern Western Diet has been associated with the rise in metabolic and inflammatory diseases, including obesity, diabetes, and cardiovascular disease. This has been attributed, in part, to the increase in dietary omega-6 polyunsaturated fatty acid (PUFA) consumption, specifically linoleic acid (LA), arachidonic acid (ARA), and their subsequent metabolism to pro-inflammatory metabolites which may be driving human disease. Conversion of dietary LA to ARA is regulated by genetic variants near and within the fatty acid desaturase (FADS) haplotype block, most notably single nucleotide polymorphism rs174537 is strongly associated with FADS1 activity and expression. This variant and others within high linkage disequilibrium may potentially explain the diversity in both diet and inflammatory mediators that drive chronic inflammatory disease in human populations. Mechanistic exploration into this phenomenon using human hepatocytes is limited by current two-dimensional culture models that poorly replicate in vivo functionality. Therefore, we aimed to develop and characterize a three-dimensional hepatic construct for the study of human PUFA metabolism. Primary human hepatocytes cultured in 3D hydrogels were characterized for their capacity to represent basic lipid processing functions, including lipid esterification, de novo lipogenesis, and cholesterol efflux. They were then exposed to control and LA-enriched media and reproducibly displayed allele-specific metabolic activity of FADS1, based on genotype at rs174537. Hepatocytes derived from individuals homozygous with the minor allele at rs174537 (i.e., TT) displayed the slowest metabolic conversion of LA to ARA and significantly reduced FADS1 and FADS2 expression. These results support the feasibility of using 3D human hepatic cultures for the study of human PUFA and lipid metabolism and relevant gene-diet interactions, thereby enabling future nutrition targets in humans. [ABSTRACT FROM AUTHOR]

The evaluation of a patient after Crotalinae envenomation requires assessment of local and systemic signs and symptoms in conjunction with laboratory data. Point-of-care ultrasound (POCUS) is an emerging modality used to evaluate soft tissue changes associated with snake envenomations around the world. However, more data are needed to characterize sonographic findings of snake envenomation. Our study used POCUS to evaluate the depth of soft tissue injury, involvement of the muscles/tendons, and the proximal edge of envenomation. This was a prospective observational study evaluating the sonographic characteristics of Crotalinae envenomation. The eight patients enrolled in the study included one envenomated by a Western diamondback (Crotalus atrox), and the others were envenomated by copperheads (Agkistrodon contortrix). All the patients demonstrated initial subcutaneous cobblestoning on POCUS at the bite site. All digit envenomations revealed edema in the tendon or tendon sheath. None of these cases required acute surgical intervention. There were no sonographic signs of envenomation found below fascia or muscle. Four of the eight patients had POCUS findings of cobblestoning proximal to the edge of envenomation palpated on the extremity. The clinical significance of this is unknown. [ABSTRACT FROM AUTHOR]

Recent recognition of "massive" acetaminophen (APAP) overdoses has led to the question of whether standard dosing of N-acetylcysteine (NAC) is adequate to prevent hepatoxicity in these patients. The primary aim of this study was to evaluate the clinical outcome for patients with massive APAP overdose who received standard intravenous NAC dosing of 300 mg/kg over 21 h. This was a single-center retrospective cohort study conducted by chart review of APAP overdoses reported to a regional poison center from 1 January 2010 to 31 December 2019. Massive APAP overdose was defined by single, acute overdose resulting in an APAP concentration exceeding 300 mcg/mL at 4 h post-ingestion. Standard univariate statistical analysis was conducted to describe the cohort, and a multivariate logistic model was utilized to calculate adjusted odds ratios for risk of hepatoxicity. 1425 cases of APAP overdose were reviewed. 104 cases met the inclusion criteria of massive APAP overdose. Overall, 79 cases (76%) had no acute liver injury or hepatotoxicity, and 25 (24%) developed hepatoxicity. Nine percent (n = 4) of cases receiving NAC within 8 h developed hepatotoxicity. Crude odds for hepatoxicity was 5.5-fold higher for cases who received NAC after 8 h. Standard NAC dosing received within 8 h prevented hepatoxicity in 91% (n = 40) of cases in our series of massive APAP overdoses. Additional data is needed to determine the clinical outcomes of massive APAP overdose using current intravenous NAC dosing. [ABSTRACT FROM AUTHOR]

We examine heat transport carried by acoustic phonons in the systems composed of nanoscale chains of masses coupled to two thermal baths of different temperatures. Thermal conductance is obtained by using linearized Landauer-type formula for heat flux with phonon transmission probability calculated within atomistic Green's functions (AGF) method. AGF formalism is extended onto dissipative chains of masses with harmonic coupling beyond nearest-neighbor approximation, while atomistic description of heat reservoirs is also included into computational scheme. In particular, the phonon lifetimes and the phonon frequency shifts are discussed for harmonic lattices of different dimensions. Further, resonant structure of phonon transmission spectrum is analyzed with respect to reservoir-induced effects, molecular damping, and mass-to-mass harmonic coupling. Analysis of transmission zeros (antiresonances) and their accompanied Fano-shape resonances are discussed as a result of interference effects between different vibrational modes. Finally, we also predict subdiffusive transport regime for low-frequency ballistic phonons propagated along a linear chain of harmonically coupled masses. [ABSTRACT FROM AUTHOR]

DNA double-strand breaks (DSBs) trigger transient pausing of nearby transcription, an emerging ATM-dependent response that suppresses chromosomal instability. We screened a chemical library designed to target the human kinome for new activities that mediate gene silencing on DSB-flanking chromatin, and have uncovered the DYRK1B kinase as an early respondent to DNA damage. We showed that DYRK1B is swiftly and transiently recruited to lasermicroirradiated sites, and that genetic inactivation of DYRK1B or its kinase activity attenuated DSB-induced gene silencing and led to compromised DNA repair. Notably, global transcription shutdown alleviated DNA repair defects associated with DYRK1B loss, suggesting that DYRK1B is strictly required for DSB repair on active chromatin. We also found that DYRK1B mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2. Together, our findings unveil the DYRK1B signaling network as a key branch of mammalian DNA damage response circuitries, and establish the DYRK1B-EHMT2 axis as an effector that coordinates DSB repair on transcribed chromatin. [ABSTRACT FROM AUTHOR]

This duoethnography describes a story of the psychological, emotional, and social impacts of recurrent miscarriage. The silence in the literature shouts for the need of research in this area. While miscarriage is an area of focus in the literature, it is our belief that recurrent miscarriage brings different dimensions of grief and challenges. We use critical inquiry and social constructionism paradigms to make sense of our experiences. Readers are expected to be active participants in our duoethnography. [ABSTRACT FROM AUTHOR]

To evaluate the clinical impact of the Canadian criteria for identifying patients and families at risk for hereditary renal cell carcinoma (RCC). The Canadian hereditary RCC risk criteria were applied to patients from 16 centres in the Canadian Kidney Cancer information system (CKCis) prospective database. The primary end point was the proportion of patients who met at least one criterion. Between January 2011 and May 2017, 8388 patients were entered in the database; 291 had inadequate risk data; 2827 (35%) met at least one criterion for genetic testing (at-risk population). Most (83%) met just one criterion. The criterion of non-clear cell histology contributed the largest proportion of at-risk patients (59%), followed by age ≤ 45 years (28%). Sixty-one patients had documentation of genetic testing, with 56 being classified at-risk (2% of at-risk). Twenty patients (35%) of the patients at risk and tested for hereditary RCC were found to harbour a germline mutation. Application of the Canadian hereditary RCC risk criteria to a large prospective database resulted in 35% of patients being identified at risk for hereditary RCC who could qualify for genetic testing. However, the true incidence of hereditary RCC in this population is unknown as most patients did not have documented genetic testing carried out and, thus, the sensitivity and specificity of the criteria cannot be determined. The low proportion of at-risk patients who underwent genetic testing is disappointing and highlights that there may be gaps in reporting, knowledge and/or barriers in access to genetic testing. • 2827 patients (35% of patients diagnosed with RCC) met the criteria for at risk for hereditary RCC. • 56 of the patients at risk were tested and 35% of them were found to harbour a germline mutation. • Low proportion of at-risk patients were referred for genetic testing. • Research is warranted to identify barriers to referrals and testing. [ABSTRACT FROM AUTHOR]

Citation data have remained hidden behind proprietary, restrictive licensing agreements, which raises barriers to entry for analysts wishing to use the data, increases the expense of performing large-scale analyses, and reduces the robustness and reproducibility of the conclusions. For the past several years, the National Institutes of Health (NIH) Office of Portfolio Analysis (OPA) has been aggregating and enhancing citation data that can be shared publicly. Here, we describe the NIH Open Citation Collection (NIH-OCC), a public access database for biomedical research that is made freely available to the community. This dataset, which has been carefully generated from unrestricted data sources such as MedLine, PubMed Central (PMC), and CrossRef, now underlies the citation statistics delivered in the NIH iCite analytic platform. We have also included data from a machine learning pipeline that identifies, extracts, resolves, and disambiguates references from full-text articles available on the internet. Open citation links are available to the public in a major update of iCite (). [ABSTRACT FROM AUTHOR]

Background: Along with alcohol, cannabis is one of the most commonly used substances among women of childbearing age. Recent studies indicate detrimental effects of prenatal cannabis use. Because many women use these substances before realizing they are pregnant, these serious health consequences for women and their offspring are of great concern. Despite the recent upsurge in cannabis use, little is known about individual and sociocultural factors that may contribute to risk of a cannabis-exposed pregnancy, particularly among Latinas of child-bearing age also at risk of an alcohol-exposed pregnancy (AEP). Objectives: Examine the relationships of acculturation, alcohol use, alcohol problems, and psychological distress with frequency of cannabis use among adult Latinas at risk of an AEP. Methods: The hypothesized model included 76 Latinas and was analyzed using path analysis. The study used baseline data from a randomized controlled trial of an intervention targeting risky drinking and tobacco use among women at risk of an AEP in primary care clinics. Results: Greater acculturation was associated with more frequent cannabis use and greater psychological distress. There was a positive indirect relationship between acculturation and alcohol use and alcohol problems through psychological distress. Greater alcohol problems were associated with more frequent cannabis use. Greater psychological distress and alcohol use were indirectly related to more frequent cannabis use through alcohol problems. Conclusions: Findings underscore the critical role of acculturation and alcohol-related problems in cannabis use frequency and have relevant implications for preventive efforts addressing cannabis use among Latinas at risk of an AEP. [ABSTRACT FROM AUTHOR]

Scientific societies aim to provide a collective voice and unified stance on important issues. The Clinical Toxicology Recommendations Collaborative was formed in 2016 to develop evidence- and consensus-based recommendations for the management of patients exposed to common and/or serious poisonings for which the management is unclear or controversial. The Clinical Toxicology Recommendations Collaborative is led jointly by the American Academy of Clinical Toxicology, the Asia Pacific Association of Medical Toxicology, and the European Association of Poison Centres and Clinical Toxicologists. The Governance Committee is chaired by a Past-President of one of these Societies and comprised of the six Presidents and Immediate Past-Presidents of the three Societies. A Steering Committee oversees the process of each project workgroup. The overall process is guided by standards set forth by the Institute of Medicine for developing trustworthy guidelines and the Appraisal of Guidelines for Research and Evaluation Instrument. Systematic reviews are produced using the framework set in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Workgroup members jointly review the evidence and prepare statements on which they vote anonymously using a 9-point Likert scale. A two-round modified Delphi method is used to reach a consensus on clinical recommendations using the RAND/UCLA Appropriateness Method. Final recommendations are approved by unanimous consent of the workgroup and are expressed as both levels of evidence and strength of recommendations. The major limitations of the Clinical Toxicology Recommendations Collaborative process centre around the amount and quality of evidence, the assessment of that evidence, and the voting of the panel. By using a transparent evidence- and consensus-based approach to produce systematic reviews and clinical recommendations, the Clinical Toxicology Recommendations Collaborative aims to create an international framework for clinical toxicology education and decision-making and foster positive change for the benefit of poisoned patients. [ABSTRACT FROM AUTHOR]

Clonidine is a central alpha-2 agonist well known to produce a syndrome of bradycardia and hypotension in overdose. However, few examples of overt clinical clonidine toxicity secondary to cutaneous absorption have been reported. We report a case of unintentional systemic clonidine toxicity in an adult because of a compounded preparation of clonidine applied to a degraded skin barrier. A 35-year-old male suffered a motorcycle accident 48 hours before presentation resulting in an abrasion to his distal left leg. On the day of presentation, he self-treated the wound by repeated application of a family member's pain-relieving cream. Later he was found confused and unable to stand by a family member. The family member recognized the thick visible coat of cream as the likely cause and decontaminated the patient while calling 911. Prehospital vitals were notable for a blood pressure of 80/30 mm Hg and heart rate of 38 beats per minute. In the emergency department, the patient was resuscitated with intravenous fluids with resultant normalization of blood pressure. Upon later review, the cream was determined to have been created by a local compounding pharmacy for the use in neuropathic pain and was labeled to contain clonidine, lidocaine, ketamine, and gabapentin. Cutaneous absorption of the pain cream was greatly increased because of loss of skin integrity. Military physicians and compounding pharmacies should ensure that patients are aware of the proper application of compounded creams and the potential risk for systemic toxicity with overuse or degraded skin. [ABSTRACT FROM AUTHOR]

Abstract We examined why the lower Little Colorado River (LCR), Arizona continues to be dominated by four native fish species despite decades of encroachment by nine nonnative species. Most perennial flow begins at Blue Spring, located at river kilometer (RKM) 20.74 above the LCR's mouth, which is supplemented downriver by other springs. Blue Spring's water is extremely supersaturated with dissolved CO2 (658 mg/L), and at baseflow the CO2 concentrations apparently functioned as a fish-barrier for about 1 km further downriver until it outgassed to 288 mg/L. Thereafter, CO2 outgassed to 202 mg/L by the top of Chute Falls (RKM 14.20) and 76 mg/L near the river's mouth. Chute Falls, and high CO2 levels above it, obstruct upriver, but not downriver, fish movements; however, we still captured fishes from eight nonnative species above this falls. Our findings indicate most warmwater nonnative fishes in the LCR were immigrants from upriver sources within and bordering the intermittent corridor that invaded the system during floods, while most coldwater trout invaded from the Colorado River. Most nonnative species failed or were severely limited at reproducing progeny in the LCR, except occasionally by channel catfish Ictalurus punctatus and fathead minnow Pimephales promelas in the lower 13.57 km corridor, which was likely related to CO2. Correlation tests suggested severe flood and/or suspended sediment regimes reduced populations of fathead minnows, red shiners Cyprinella lutrensis, and plains killifish Fundulus zebrinus in the LCR. Conversely, severe suspended sediment regimes (especially ≥60,000 mg/L) increased channel catfish, black bullhead Ameiurus melas, and common carp Cyprinus carpio, hypothetically by paralyzing these fishes upriver, whereby many drifted downstream and recovered in the lower LCR; however, their abundances decreased after prolonged periods of high CO2. Nonnative fishes are controlled in the LCR by the system's endemic abiotic conditions. [ABSTRACT FROM AUTHOR]

The physical environment of the stadium may have a significant effect on the extent to which spectators will desire to stay and return to the stadium. Specific aspects of the stadium experience may lead directly to spectators' pleasure with the place, while other factors may contribute to negative feelings that may decrease pleasure. This study provides sports facility managers with a reliable survey instrument to determine how spectators perceive their facility. Recommendations are provided to guide stadium owners and managers in the effective management of the facility to maximize spectator satisfaction. [ABSTRACT FROM AUTHOR]

Having loyal fans and a winning team generally results in higher attendance at games. However, university and professional team administrators are beginning to recognize the importance of marketing the stadium experience as more than just the game. Drawing from data collected from spectators at five Southeastern Conference football stadiums, the effects of team loyalty, stadium parking, stadium cleanliness, perceived crowding, food service, and fan behavior control on spectators' desire to stay and attend games at the stadium were investigated. Covariance structural modeling (e.g., LISREL) was employed to test the causal relationships among the hypothesized relationships. The results support the premise that although team loyalty strongly affects attendance, stadium design and stadium services also directly influence spectators' desire to stay. and hence, attend games at the stadium. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to examine the reliability of the isometric midthigh pull (IMTP) and the relationship between IMTP peak force and deadlift 1 repetition maximum (1RM). Nine subjects (5 men and 4 women; 40.6 ± 8.0 years; 1.72 ± 0.10 m; 75.6 ± 13.4 kg) participated in this study. Isometric midthigh pull and deadlift 1RM were both performed during 2 testing sessions. For IMTP, peak force and peak rate of force development (RFD) were determined, in addition to RFD at 30 ms, 50 ms, 90 ms, 150 ms, 200 ms, and 250 ms after initiation of the pull. Intraclass correlation coefficients (ICCs) were calculated to evaluate the reliability of IMTP measures. Pearson product-moment correlations and linear regression were used to determine associations between IMTP and deadlift 1RM. Isometric midthigh pull peak force was reproducible both within (ICC = 0.98 and 0.97) and between sessions (ICC = 0.89) and significantly correlated with deadlift 1RM (r = 0.88, p ≤ 0.05), but intermediate force outputs and RFD were not. Lack of associations between RFD and deadlift 1RM indicate that the ability to create explosive force may be independent of the ability to create maximal force. The strong relationship between IMTP peak force and deadlift 1RM was present regardless of which IMTP repetition across the 2 sessions was examined. Peak force generated during IMTP is a reliable method to assess full body maximal strength. A single IMTP repetition, provided adequate familiarization and warm-up, correlates strongly with deadlift 1RM. Practitioners can use the IMTP test as a method to estimate maximal deadlift strength in a quick and potentially less provocative manner than traditional 1RM testing. [ABSTRACT FROM AUTHOR]

Background: Phenotyping technologies featured in the diagnosis of inborn errors of metabolism, such as organic acid, amino acid, and acylcarnitine analyses, recently have been supplemented by broad-scale untargeted metabolomic phenotyping. We investigated the analyte changes associated with aromatic amino acid decarboxylase (AADC) deficiency and dopamine medication treatment.Methods: Using an untargeted metabolomics platform, we analyzed ethylenediaminetetraacetic acid plasma specimens, and biomarkers were identified by comparing the biochemical profile of individual patient samples to a pediatric-centric population cohort.Results: Elevated 3-methoxytyrosine (average z score 5.88) accompanied by significant decreases of dopamine 3-O-sulfate (-2.77), vanillylmandelate (-2.87), and 3-methoxytyramine sulfate (-1.44) were associated with AADC deficiency in three samples from two patients. In five non-AADC patients treated with carbidopa-levodopa, levels of 3-methoxytyrosine were elevated (7.65); however, the samples from non-AADC patients treated with DOPA-elevating drugs had normal or elevated levels of metabolites downstream of aromatic l-amino acid decarboxylase, including dopamine 3-O-sulfate (2.92), vanillylmandelate (0.33), and 3-methoxytyramine sulfate (5.07). In one example, a plasma metabolomic phenotype pointed to a probable AADC deficiency and prompted the evaluation of whole exome sequencing data, identifying homozygosity for a known pathogenic variant, whereas whole exome analysis in a second patient revealed compound heterozygosity for two variants of unknown significance.Conclusions: These data demonstrate the power of combining broad-scale genotyping and phenotyping technologies to diagnose inherited neurometabolic disorders and suggest that metabolic phenotyping of plasma can be used to identify AADC deficiency and to distinguish it from non-AADC patients with elevated 3-methoxytyrosine caused by DOPA-raising medications. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol and tobacco use are common among U.S. women, yet if used during pregnancy these substances present significant preventable risks to prenatal and perinatal health. Because use of alcohol and tobacco often continue into the first trimester and beyond, especially among women with unintended pregnancies, effective evidence-based approaches are needed to decrease these risk behaviors. This study was designed to test the efficacy of CHOICES Plus, a preconception intervention for reducing the risk of alcohol- and tobacco-exposed pregnancies (AEPs and TEPs).Study Design: RCT with two intervention groups: CHOICES Plus (n=131) versus Brief Advice (n=130). Data collected April 2011 to October 2013. Data analysis finalized February 2016.Setting/participants: Settings were 12 primary care clinics in a large Texas public healthcare system. Participants were women who were non-sterile, non-pregnant, aged 18-44 years, drinking more than three drinks per day or more than seven drinks per week, sexually active, and not using effective contraception (N=261). Forty-five percent were smokers.Intervention: Interventions were two CHOICES Plus sessions and a contraceptive visit or Brief Advice and referral to community resources.Main Outcome Measures: Primary outcomes were reduced risk of AEP and TEP through 9-month follow-up.Results: In intention-to-treat analyses across 9 months, the CHOICES Plus group was more likely than the Brief Advice group to reduce risk of AEP with an incidence rate ratio of 0.620 (95% CI=0.511, 0.757) and absolute risk reduction of -0.233 (95% CI=-0.239, -0.226). CHOICES Plus group members at risk for both exposures were more likely to reduce TEP risk (incidence rate ratio, 0.597; 95% CI=0.424, 0.840 and absolute risk reduction, -0.233; 95% CI=-0.019, -0.521).Conclusions: CHOICES Plus significantly reduced AEP and TEP risk. Addressing these commonly co-occurring risk factors in a single preconception program proved both feasible and efficacious in a low-income primary care population. Intervening with women before they become pregnant could shift the focus in clinical practice from treatment of substance-exposed pregnancies to prevention of a costly public health concern.Trial Registration: This study is registered at clinicaltrials.gov NCT01032772. [ABSTRACT FROM AUTHOR]

We sought to determine the molecular composition of human cerebrospinal fluid (CSF) and identify the biochemical pathways represented in CSF to understand the potential for untargeted screening of inborn errors of metabolism (IEMs). Biochemical profiles for each sample were obtained using an integrated metabolomics workflow comprised of four chromatographic techniques followed by mass spectrometry. Secondarily, we wanted to compare the biochemical profile of CSF with those of plasma and urine within the integrated mass spectrometric-based metabolomic workflow. Three sample types, CSF (N = 30), urine (N = 40) and EDTA plasma (N = 31), were analyzed from retrospectively collected pediatric cohorts of equivalent age and gender characteristics. We identified 435 biochemicals in CSF representing numerous biological and chemical/structural families. Sixty-three percent (273 of 435) of the biochemicals detected in CSF also were detected in urine and plasma, another 32% (140 of 435) were detected in either plasma or urine, and 5% (22 of 435) were detected only in CSF. Analyses of several metabolites showed agreement between clinically useful assays and the metabolomics approach. An additional set of CSF and plasma samples collected from the same patient revealed correlation between several biochemicals detected in paired samples. Finally, analysis of CSF from a pediatric case with dihydropteridine reductase (DHPR) deficiency demonstrated the utility of untargeted global metabolic phenotyping as a broad assessment to screen samples from patients with undifferentiated phenotypes. The results indicate a single CSF sample processed with an integrated metabolomics workflow can be used to identify a large breadth of biochemicals that could be useful for identifying disrupted metabolic patterns associated with IEMs. [ABSTRACT FROM AUTHOR]

We describe a process for evaluating proposed ecosystem restoration projects intended to improve survival of juvenile salmon in the Columbia River estuary (CRE). Changes in the Columbia River basin (northwestern USA), including hydropower development, have contributed to the listing of 13 salmon stocks as endangered or threatened under the U.S. Endangered Species Act. Habitat restoration in the CRE, from Bonneville Dam to the ocean, is part of a basin-wide, legally mandated effort to mitigate federal hydropower impacts on salmon survival. An Expert Regional Technical Group (ERTG) was established in 2009 to improve and implement a process for assessing and assigning “survival benefit units” (SBUs) to restoration actions. The SBU concept assumes site-specific restoration projects will increase juvenile salmon survival during migration through the 234 km CRE. Assigned SBUs are used to inform selection of restoration projects and gauge mitigation progress. The ERTG standardized the SBU assessment process to improve its scientific integrity, repeatability, and transparency. In lieu of experimental data to quantify the survival benefits of individual restoration actions, the ERTG adopted a conceptual model composed of three assessment criteria—certainty of success, fish opportunity improvements, and habitat capacity improvements—to evaluate restoration projects. Based on these criteria, an algorithm assigned SBUs by integrating potential fish density as an indicator of salmon performance. Between 2009 and 2014, the ERTG assessed SBUs for 55 proposed projects involving a total of 181 restoration actions located across 8 of 9 reaches of the CRE, largely relying on information provided in a project template based on the conceptual model, presentations, discussions with project sponsors, and site visits. Most projects restored tidal inundation to emergent wetlands, improved riparian function, and removed invasive vegetation. The scientific relationship of geomorphic and salmonid responses to restoration actions remains the foremost concern. Although not designed to establish a broad strategy for estuary restoration, the scoring process has adaptively influenced the types, designs, and locations of restoration proposals. The ERTG process may be a useful model for others who have unique ecosystem restoration goals and share some of our common challenges. [ABSTRACT FROM AUTHOR]

ABSTRACT This study characterizes the metabolic profile of synovial fluid after intra-articular ankle fracture with an emphasis on changes in the lipid profile. Bilateral ankle synovial fluid from 19 patients with unilateral intra-articular ankle fracture was submitted for metabolic profiling. Contralateral ankle synovial fluid from each patient served as a matched control. Seven patients participated in a second bilateral synovial fluid collection after 6 months. Random forest classification, matched pairs t-tests ( α < 0.01), repeated measures ANOVA with post-test contrasts ( α < 0.01), correlation to cytokines and matrix metalloproteinases, and fracture and injury classification analyses yielded key lipid biomarkers in synovial fluid following intra-articular fracture. Free fatty acids, sphingomyelins, and lysolipids demonstrated significant elevation in fractured ankles at baseline. Fatty acids and sphingomyelins showed a significant decrease 6 months post-surgery. Random forest analysis showed predominantly fatty acids differentiating between groups. Significant correlations included fatty acids, sphingomyelins, and lysolipids with inflammatory cytokines and matrix metalloproteinases. Fracture classification showed increased fatty acids, lysolipids, and inositol metabolites as fracture severity increased. Fatty acid and sn-1 lysolipid elevation could be detrimental to the joint, as these strongly correlated with matrix metalloproteinases and TNF-α. This elevation also suggests involvement of phospholipase A2, a potential target for therapeutic intervention. Together with elevated 2-hydroxyl fatty acids, these findings suggest elevated sn-1 lysolipids, sphingomyelins, and subsequent lipid metabolites in synovial fluid as biomarkers of ankle injury. Reversal of this signature after 6 months suggests temporary involvement of these metabolites in disease progression, although they may activate signaling pathways which drive progression to osteoarthritis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:657-666, 2017. [ABSTRACT FROM AUTHOR]

Background:Salicylate absorption following overdose of aspirin (ASA) tablet formulations can be prolonged for greater than 24 h. Accordingly, serial serum concentrations are typically recommended to guide treatment. However, there are little published data on absorption following ingestion of powder ASA formulations, and it is not known if delayed ASA absorption occurs following overdose of powder formulations. The objective of this study is to compare the absorption characteristics of powder and tablet formulations of ASA in patients reported to a single poison center. Methods:Electronic records from an accredited poison center were searched for single substance acute or acute on chronic ingestions of ASA in powder form between 1 January 2002 and 31 January 2014. An identical search for ingestions of ASA tablet products between 1 January 2012 and 31 December 2013 was undertaken as the comparator group. Other inclusion criteria were age >12 years, documented time of ingestion, treatment in a health care facility within nine hours of ingestion and at least two detectable serum salicylate concentrations. Results:16 of 25 powder and 22 of 49 tablet cases met inclusion criteria for analysis. Repeat serum salicylate concentrations following ingestion of tablets increased or insignificantly changed in 11 of 22 (50%) cases, and median serum salicylate concentrations in followed cases remained elevated for up to 12 h in some cases. In comparison, serum salicylate concentrations following powder ingestions declined in 15 of 16 (94%) cases. One patient, who ingested a powder product, underwent hemodialysis pursuant to an initial serum salicylate concentration of 96 mg/dL. Conclusions:In contrast to persistent concentrations following overdose of tablets, the majority of serum salicylate concentrations declined following ingestion of powder formulations. In this small study population, these findings suggest that prolonged absorption is unlikely following ingestions of ASA powders. [ABSTRACT FROM AUTHOR]

Technical advancements in research techniques in science are made in slow increments. Even so, large advances from insight and hard work of an individual with a single technique can have astonishing ramifications. Here, we examine the impact of Dr. Maurice B. Burg and the isolated perfused renal tubule technique and celebrate the 50th anniversary of the publication by Dr. Burg and his colleagues of their landmark paper in the American Journal of Physiology in 1966. In this study, we have taken a scientific visualization approach to study the scientific contributions of Dr. Burg and the isolated perfused tubule preparation as determining research impact by the number of research students, postdoctoral fellows, visiting scientists, and national and international collaborators. Additionally, we have examined the research collaborations (first and second generation scientists), established the migrational visualization of the first generation scientists who worked directly with Dr. Burg, quantified the metrics indices, identified and quantified the network of coauthorship of the first generation scientists with their second generation links, and determined the citations analyses of outputs of Dr. Burg and/or his first generation collaborators as coauthors. We also review the major advances in kidney physiology that have been made with the isolated perfused tubule technique. Finally, we are all waiting for the discoveries that the isolated perfused preparation technique will bring during the next 50 years. [ABSTRACT FROM AUTHOR]

Small differences in amplitude, duration, and temporal patterns of change in the concentration of free intracellular Ca[sup 2+] ([Ca[sup 2+]][sub i]) can profoundly affect cell physiology, altering programs of gene expression, cell proliferation, secretory activity, and cell survival. We report a novel mechanism for amplitude modulation of [Ca[sup 2+]][sub i] that involves mitogen-activated protein kinase (MAPK). We show that epidermal growth factor (EGF) potentiates gastrin-(1-17) (G17)-stimulated Ca[sup 2+] release from intracellular Ca[sup 2+] stores through a MAPK-dependent pathway. G17 activation of the cholecystokinin/gastrin receptor (CCK[sub 2]R), a G protein-coupled receptor, stimulates release of Ca[sup 2+] from inositol 1,4,5-triphosphate-sensitive Ca[sup 2+] stores. Pretreating rat intestinal epithelial cells expressing CCK[sub 2]R with EGF increased the level of G17-stimulated Ca[sup 2+] release from intracellular stores. The stimulatory effect of EGF on CCK[sub 2]Rmediated Ca[sup 2+] release requires activation of the MAPK kinase (MEK)1,2/extracellular signal-regulated kinase (ERK)1,2 pathway. Inhibition of the MEK1,2/ERK1,2 pathway by either serum starvation or treatment with selective MEK1,2 inhibitors PD98059 and U0126 or expression of a dominant-negative mutant form of MEK1 decreased the amplitude of the G17-stimulated Ca[sup 2+] release response. Activation of the MEK1,2/ERK1,2 pathway either by pretreating cells with EGF or by expression of constitutively active K-ras (K-rasV12G) or MEK1 (MEK1[sup *]) increased the amplitude of G17-stimulated Ca[sup 2+] release. Although EGF, MEK1[sup *], and K-rasV12G activated the MEK1,2/ERK1,2 pathway, they did not increase [Ca[sup 2+]][sub i] in the absence of G17. These data demonstrate that the activation state of the MEK1,2/ERK1,2 pathway can modulate the amplitude of the CCK[sub 2]R-mediated Ca[sup 2+] release response and identify a novel mechanism for cross-talk between EGF receptor- and CCK[sub 2]Rregulated signaling pathways. [ABSTRACT FROM AUTHOR]

The productivity of semiarid Australian grassland ecosystems is currently limited by water availability and may be impacted further by predicted changes in rainfall regimes associated with climate change. In this study, we established a rainfall manipulation experiment to determine the effects of reduced frequency (RF; 8 days between water events) and reduced magnitude (RM; 50% reduction in amount) of rainfall events on the physiology and above- and belowground growth of five grassland plant species with differing traits. Native C4 grasses exhibited the highest productivity in well watered, control (Cont) conditions, as well as in RF and RM treatments. The RF treatment generally had little effect on total biomass, rooting distributions or photosynthesis, suggesting species were relatively tolerant of reduction in the frequency of rainfall events. However, the RM treatment had a negative effect on total biomass and physiology, and generally resulted in a shift towards shallower rooting profiles. Overall, the reduction in biomass was greater in RM than RF, suggesting that rainfall magnitude may be a more important determinant of grassland productivity and composition than the frequency of rainfall events under future climates. [ABSTRACT FROM AUTHOR]

The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery. [ABSTRACT FROM AUTHOR]

The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery. [ABSTRACT FROM AUTHOR]

We consider phononic energy transport between nanoparticles mediated by a quantum particle. The nanoparticles are considered as thermal reservoirs described by ensembles of finite numbers of harmonic oscillators within the Drude-Ullersma model having, in general, unequal mode spacings Δ1 and Δ2, which amount to different numbers of atoms in the nanoparticles. The quasistatic energy transport between the nanoparticles on the time scale t ~ 1/Δ1,2 is investigated using the generalized quantum Langevin equation. We find that double degeneracy of system's eigenfrequencies, which occurs in the case of identical nanoparticles, is removed when the mode spacings become unequal. The equations describing the dynamics of the averaged eigenmode energies are derived and solved, and the resulting expression for the energy current between the nanoparticles is obtained and explored. Unlike the case when the thermodynamic limit is assumed resulting in time-independent energy current, finite-size effects result in temporal behavior of the energy current that evinces reversibility features combined with decay and possesses peculiarities at time moments t = 2πn/Δ1 + 2πm/Δ2 for non-negative integers n and m. When Δ1,2 0, an expression for the heat current obtained previously under assumption of the thermodynamic limit is reproduced. The energy current between two platinum nanoparticles mediated by a carbon oxide molecule is considered as an application of the developed model. [ABSTRACT FROM AUTHOR]

In Drosophila photoreceptors, the NINAC-encoded myosin III is found in a complex with a small, MORN-repeat containing, protein Retinophilin (RTP). Expression of these two proteins in other cell types showed NINAC myosin III behavior is altered by RTP. NINAC deletion constructs were used to map the RTP binding site within the proximal tail domain of NINAC. In vertebrates, the RTP ortholog is MORN4. Co-precipitation experiments demonstrated that human MORN4 binds to human myosin IIIA (MYO3A). In COS7 cells, MORN4 and MYO3A, but not MORN4 and MYO3B, co-localize to actin rich filopodia extensions. Deletion analysis mapped the MORN4 binding to the proximal region of the MYO3A tail domain. MYO3A dependent MORN4 tip localization suggests that MYO3A functions as a motor that transports MORN4 to the filopodia tips and MORN4 may enhance MYO3A tip localization by tethering it to the plasma membrane at the protrusion tips. These results establish conserved features of the RTP/MORN4 family: they bind within the tail domain of myosin IIIs to control their behavior. [ABSTRACT FROM AUTHOR]

Ethanolic extracts of three different varieties of purple maize ( Zea mays L.) were examined for scavenging activities toward nitric oxide (NO ) and superoxide ( ·O 2 − ) and the ability to induce quinone reductase (QR). The crude extracts showed a dose-dependent antioxidant activity in the following order: generic purple > Oaxaca 332 > Veracruz 42. The extract of the generic purple variety exhibited the highest ability to induce QR activity and antioxidant activity was split into several fractions that showed antioxidant activities and capacity for doubling QR specific activity. Fraction III doubled QR at a content of 105 μg/mL (CD value). Semi-preparative LC and UV spectral and MS analyses of fraction III indicated the presence of glucosidic forms of cyanidin, peonidin, pelargonidin and their respective acylated counterparts. [ABSTRACT FROM AUTHOR]

Long-duration spaceflight results in muscle atrophy and a loss of bone mineral density. In skeletal muscle tissue, acute exercise and protein (e.g., essential amino acids) stimulate anabolic pathways (e.g., muscle protein synthesis) both independently and synergistically to maintain neutral or positive net muscle protein balance. Protein intake in space is recommended to be 12%-15% of total energy intake (≥1.4 g⋅kg-1day-1) and spaceflight is associated with reduced energy intake (~20%), which enhances muscle catabolism. Increasing protein intake to 1.5-2.0 g⋅kg-1day-1 may be beneficial for skeletal muscle tissue and could be accomplished with essential amino acid supplementation. However, increased consumption of sulfur-containing amino acids is associated with increased bone resorption, which creates a dilemma for musculoskeletal countermeasures, whereby optimizing skeletal muscle parameters via essential amino acid supplementation may worsen bone outcomes. To protect both muscle and bone health, future unloading studies should evaluate increased protein intake via non-sulfur containing essential amino acids or leucine in combination with exercise countermeasures and the concomitant influence of reduced energy intake. [ABSTRACT FROM AUTHOR]